Tocilizumab Improved Periodontal, Rheumatologic Parameters in Patients With RA

Patients with rheumatoid arthritis (RA) and comorbid periodontitis experienced significant improvement in periodontal inflammation following treatment with tocilizumab, according to a study published online in November 2015 in Clinical and Experimental Dental Research.¹ Tocilizumab (TCZ) is a recombinant humanized antihuman interleukin-6 receptor (IL-6R) monoclonal antibody. In the United States, TCZ is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response to treatment with one or more tumor necrosis factor (TNF) antagonists.²

Periodontitis and Rheumatoid Arthritis Commonalities

A substantial body of literature strongly suggests that periodontitis and RA share epidemiologic, clinical, and pathogenic commonalities. Periodontitis is twice as prevalent and twice as severe in patients with RA, and patients with RA are more likely to have periodontitis than those without RA. Chronic inflammation has deleterious effects on bone metabolism and bone architecture in both RA and periodontal disease, and the mechanism underlying alveolar resorption resembles the mechanism that underlies joint erosions. Both diseases share a similarly dysregulated profile of inflammatory mediators that include TNF-α, IL-1, IL-6, prostaglandin E2, reactive oxygen species, and matrix metalloproteinases (MMP).³

Study Results

The longitudinal case-control association study by Tetsuo Kobayashi and colleagues at Niiagata University in Niigata, Japan, included 60 patients from the Niigata Rheumatic Center in Shibata, Japan, with comorbid periodontitis and RA. The study’s stated purpose was to compare periodontal parameters in patients with both RA and periodontitis before and after TCZ therapy. Forty patients were selected by rheumatologists for treatment with a TNF inhibitor) and 20 for treatment with TCZ based on their clinical needs as indicated by EULAR (European League Against Rheumatism) criteria and recommendations. Treatment with a TNF inhibitor was shown in a number of previous studies to be efficacious against periodontal diseases.

Patients in both the TNF inhibitor and TCZ study arms demonstrated a significant decrease in periodontal inflammation as characterized by improvements in gingival index, probing depth, and bleeding on probing. The authors noted that these results are consistent with prior research showing the beneficial effects of TNF inhibition in periodontal disease. Neither TNF inhibitor nor TCZ significantly affected plaque levels. Patients in both arms saw improvement in rheumatologic parameters, including a significant reduction in the Disease Activity Score including 28 joints using C-reactive protein (DAS28-CRP), a measure that includes the assessment of tenderness and swelling in 28 joints typically affected in RA along with CRP; number of tender and swollen joints; scoring on a visual analogue scale (VAS); and serum levels of anti-cyclic citrullinated peptide (CCP) antibodies, rheumatoid factor, CRP, and MMP-3. Noted the authors, “These results suggest that TCZ and TNF inhibitor therapies may not only decrease RA activity but also ameliorate systemic inflammation, which may indirectly contribute to the improvement of periodontal inflammation as well.”

“The results of the present study suggest a beneficial effect of TCZ therapy on levels of periodontal inflammation in patients with RA and periodontitis, which might be related to decrease in serum inflammatory mediators,” concluded the researchers. “Further studies are necessary to determine the beneficial effect of IL-6R blockade on periodontitis in a larger group of patients and controls.”

References

1. Kobayashi T, Okada M, Ito S, et al. Assessment of interleukin-6 receptor inhibition therapy on periodontal condition in patients with rheumatoid arthritis and chronic periodontitis. J Periodontol. 2014;85(1):57-67. doi:10.1902/jop.2013.120696.
2. ACTEMRA [package insert]. South San Francisco, CA: Genentech, Inc.; 2010. http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/125276lbl.pdf.
3. Bartold PM, Marshall RI, Haynes DR. Periodontitis and rheumatoid arthritis: a review. J Periodontol. 2005;76(11-s):2066-2074. doi:10.1902/jop.2005.76.11-S.2066.